Overview
Definition:
Hyperglycemic hyperosmolar state (HHS) is a life-threatening metabolic derangement characterized by severe hyperglycemia, profound dehydration, and extreme hyperosmolality, typically without significant ketosis
In adolescents, it most commonly occurs in the context of new-onset type 1 diabetes or as a complication of poorly controlled type 2 diabetes, often precipitated by an underlying illness or stressor.
Epidemiology:
HHS is less common than diabetic ketoacidosis (DKA) in adolescents, but its incidence is increasing with the rise in type 2 diabetes
It is more frequently seen in older adolescents and those with underlying comorbidities
Precipitating factors include infection, non-adherence to insulin therapy, new diagnosis of diabetes, or medications like corticosteroids.
Clinical Significance:
HHS in adolescents carries a high mortality and morbidity rate if not recognized and managed promptly
Complications include neurological deficits, thrombotic events, acute kidney injury, and cardiac arrhythmias
Early diagnosis and aggressive management are crucial for preventing severe outcomes and improving patient prognosis.
Clinical Presentation
Symptoms:
Gradual onset of polyuria
Progressive polydipsia
Significant weight loss over weeks to months
Profound weakness and fatigue
Nausea and vomiting may be present but are less common than in DKA
Altered mental status, ranging from lethargy and confusion to stupor or coma
Focal neurological deficits can occur.
Signs:
Severe dehydration: dry mucous membranes, poor skin turgor, sunken eyes, tachycardia, hypotension
Tachypnea may be present but usually without Kussmaul respirations
Fever if infection is the precipitant
Neurological signs: decreased level of consciousness, focal neurological deficits (e.g., hemiparesis, aphasia), seizures
Abdominal pain can be present.
Diagnostic Criteria:
Diagnostic criteria for HHS generally include: Serum glucose > 600 mg/dL (33.3 mmol/L)
Serum osmolality ≥ 320 mOsm/kg
Arterial pH > 7.30
Bicarbonate > 15 mEq/L (15 mmol/L)
Serum ketones minimal or absent (low levels of beta-hydroxybutyrate or acetoacetate)
Anion gap usually < 10 mEq/L (10 mmol/L)
Altered level of consciousness or other neurological symptoms.
Diagnostic Approach
History Taking:
Detailed history of recent fluid intake and output
Onset and progression of symptoms
Presence of precipitating factors: infection, illness, medication use (e.g., corticosteroids, antipsychotics), trauma
Family history of diabetes
Previous episodes of hyperglycemia or DKA
Adherence to diabetes medications if diagnosed
Symptoms of underlying infection.
Physical Examination:
Assess hydration status: skin turgor, mucous membranes, capillary refill
Vital signs: heart rate, blood pressure, respiratory rate, temperature
Neurological assessment: Glasgow Coma Scale (GCS), pupillary response, focal neurological deficits
Assess for signs of infection (e.g., pharyngeal erythema, lung crackles, skin lesions)
Palpate abdomen for tenderness.
Investigations:
Laboratory tests: Serum glucose (confirm hyperglycemia)
Serum electrolytes (sodium, potassium, chloride, bicarbonate)
Blood urea nitrogen (BUN) and creatinine (assess renal function and dehydration)
Serum osmolality (calculated or measured)
Complete blood count (CBC) with differential (assess for infection)
Arterial or venous blood gas (assess acid-base status)
Serum ketone levels (beta-hydroxybutyrate or acetoacetate) to rule out significant ketosis
Urinalysis for glucose and ketones
ECG (to assess for electrolyte abnormalities, especially potassium)
Blood cultures and cultures of suspected infection sites if indicated
Imaging: Chest X-ray if pneumonia is suspected
CT head if neurological deficits are focal or to rule out stroke.
Differential Diagnosis:
Diabetic ketoacidosis (DKA): characterized by significant ketosis and metabolic acidosis
Other causes of altered mental status: sepsis, stroke, drug overdose, metabolic encephalopathy, hyponatremia
Other causes of severe hyperglycemia: pancreatitis, steroid-induced hyperglycemia, postprandial hyperglycemia
Dehydration from other causes: gastroenteritis, excessive fluid loss.
Management
Initial Management:
Aggressive fluid resuscitation is paramount
Intravenous access: establish at least one, preferably two large-bore IV lines
Fluid choice: Isotonic saline (0.9% NaCl) is the initial fluid of choice
Administer fluids rapidly to correct hypovolemia and hyperosmolality
Initial fluid bolus of 15-20 mL/kg over 1-2 hours, followed by continuous infusion based on hydration status.
Medical Management:
Insulin therapy: Once initial fluid resuscitation is underway and serum potassium is >3.3 mEq/L (3.3 mmol/L), begin continuous intravenous insulin infusion
Start with a low dose, e.g., 0.1 units/kg/hour
The goal is to reduce glucose by 50-75 mg/dL (2.8-4.2 mmol/L) per hour
Monitor glucose levels hourly
Phosphate replacement may be needed if hypophosphatemia develops
Bicarbonate therapy is generally NOT indicated unless severe acidosis is present and refractory to fluids and insulin.
Supportive Care:
Electrolyte monitoring and replacement: Closely monitor serum potassium
If hypokalemia develops, replete potassium cautiously before or during insulin infusion
Monitor sodium, phosphate, and magnesium levels and replete as needed
Neurological monitoring: Frequent assessment of mental status
Institute seizure precautions if indicated
Identify and treat precipitating factors: Aggressively treat any underlying infection
Monitor vital signs and fluid balance meticulously
Nutritional support: Once the patient is hemodynamically stable and glucose levels are improving, consider starting enteral nutrition if oral intake is not possible
Avoid rapid refeeding to prevent refeeding syndrome.
Complications
Early Complications:
Cerebral edema: the most feared complication, especially with rapid correction of hyperglycemia and osmolality
Manifests as headache, altered mental status, coma, or seizures
Hypoglycemia: if insulin infusion is too rapid or glucose monitoring is inadequate
Hypokalemia: can lead to cardiac arrhythmias
Hyperchloremic metabolic acidosis: may occur with excessive use of normal saline.
Late Complications:
Thromboembolic events: due to hyperviscosity and dehydration
Acute kidney injury: secondary to severe dehydration and hypotension
Prolonged recovery period
Recurrent episodes of HHS or DKA if diabetes management is suboptimal.
Prevention Strategies:
Education of patients and families on diabetes management, sick-day rules, and early recognition of hyperglycemia symptoms
Prompt medical attention for illness
Regular monitoring of blood glucose and adherence to insulin regimen
Avoidance of precipitating factors where possible
Close follow-up with endocrinology team.
Prognosis
Factors Affecting Prognosis:
Severity of dehydration and hyperosmolality at presentation
Degree of altered mental status
Presence of comorbidities
Promptness and adequacy of treatment
Development of complications like cerebral edema
Underlying cause of HHS.
Outcomes:
With prompt and aggressive management, most adolescents can recover from HHS
However, mortality rates can be as high as 10-20% in severe cases
Long-term morbidity includes potential neurological deficits
Successful management often requires intensive care unit (ICU) monitoring and multidisciplinary care.
Follow Up:
Close follow-up with a pediatric endocrinologist is essential
Ongoing education on diabetes self-management, including glucose monitoring, insulin administration, sick-day management, and recognition of early symptoms of hyperglycemia or dehydration
Regular assessment for complications and adjustment of treatment plan.
Key Points
Exam Focus:
HHS is characterized by severe hyperglycemia, hyperosmolality, and profound dehydration with minimal ketosis
Aggressive fluid resuscitation is the cornerstone of initial management
Monitor potassium closely before and during insulin infusion
Cerebral edema is a major complication of rapid correction.
Clinical Pearls:
Calculate serum osmolality early
Use isotonic saline for initial fluid resuscitation
Start insulin infusion at 0.1 units/kg/hr once potassium is adequate
Transition to subcutaneous insulin once glucose levels stabilize and the patient is eating
Always consider precipitating factors like infection.
Common Mistakes:
Delaying fluid resuscitation
Administering insulin before adequate rehydration or without monitoring potassium
Using hypotonic fluids too early
Failure to identify and treat precipitating infections
Aggressive correction of hyperglycemia leading to cerebral edema.